[Human embryonic stem cells. Problems and perspectives].

Establishment of human embryonic stem cell lines is one the major achievements in the biological science in the XX century and has excited a wide scientific and social response as embryonic stem cells can be regarded in future as unlimited source of transplantation materials for the replacement cell therapy. To date human embryonic cell lines are obtained in more than 20 countries. In our country the embryonic stem cell researches are carried out in the Institute of Cytology RAS and the Institute of Gene Biology RAS. ESC lines are derived from placed in culture inner cell mass of human preimplantation blastocysts used in the in vitro fertilization procedure. Studies with human ESC go in several directions. Much attention is paid to the elaboration of the optimal conditions for ESC cultivation, mainly to the development of cultivation methods excluding animal feeder cells and other components of animal origin. Another direction is a scale analysis of gene expression specific for the embryonic state of the cells and corresponding signaling pathways. Many efforts are concentrated to find conditions for the directed differentiation of ESC into different tissue-specific cells. It has been shown that ESC are able to differentiate in vitro practically into any somatic cells. Some works are initiated to develop methods for the "therapeutic cloning", that is transfer and reactivation of somatic nuclei into enucleated oocytes or embryonic stem cell cytoblasts. Of great importance is human ESC line standardization. However, the standard requirements for the cells projected for research or therapeutic purposes may be different. It has been found that many permanent human ESC lines undergo genetic and epigenetic changes and, therefore, the cell line genetic stability should be periodically verified. The main aim of the review presented is a detailed consideration of the works analyzing the genetic stability of human and mouse ESC lines. Human ESC lines established in our and as well as in other countries couldn't be used so far in clinical practice. It is highly probable that undifferentiated ESC cannot be applied for therapeutic purposes because of the risk of their malignant transformation. Therefore, main efforts should be focused on the production of progenitor and highly differentiated cells suitable for transplantation derived from ESC.